tbuckley/cabot-search huggingface dataset:
Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development
Authors: José Ricardo Vieira, Bhavin Shah, Sebastian Dupraz, Isidora Paredes, Patricia Himmels, Géza Schermann, Heike Adler, Alessia Motta, Lea Gärtner, Ariadna Navarro-Aragall, Elena Ioannou, Elena Dyukova, Remy Bonnavion, Andreas Fischer, Dario Bonanomi, Frank Bradke, Christiana Ruhrberg, Carmen Ruiz de Almodóvar
Journal: Neuron (2022)

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development.
Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice, an AD model
Authors: Chanho Kong, Eun-Jeong Yang, Jaewoo Shin, Junwon Park, Si-Hyun Kim, Seong-Wook Park, Won Seok Chang, Chang-Han Lee, Hyunju Kim, Hye-Sun Kim, Jin Woo Chang
Journal: Translational Neurodegeneration (2022)

Abstract Background Aducanumab (Adu), which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid, has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose (10 mg/kg) of the drug in Alzheimer’s disease (AD) clinical trials. The purpose of this study was to investigate the effects of a lower dose of Adu (3 mg/kg) with enhanced delivery via focused ultrasound (FUS) in an AD mouse model. Methods The FUS with microbubbles opened the blood–brain barrier (BBB) of the hippocampus for the delivery of Adu. The combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly. Y-maze test, Brdu labeling, and immunohistochemical experimental methods were employed in this study. In addition, RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental animals. Results The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the brains. The combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS alone. Combined treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD mice. Furthermore, RNA sequencing identified that 4 enriched canonical pathways including phagosome formation, neuroinflammation signaling, CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined treatment. Conclusion In conclusion, the enhanced delivery of a low dose of Adu (3 mg/kg) via FUS decreases amyloid deposits and attenuates cognitive function deficits. FUS-mediated BBB opening increases adult hippocampal neurogenesis as well as drug delivery. We present an AD treatment strategy through the synergistic effect of the combined therapy of FUS and Adu.
M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3
Authors: Lamei Huang, Fang Wang, Xueping Wang, Chaoyue Su, Shaocong Wu, Chuan Yang, Min Luo, Jianye Zhang, Liwu Fu
Journal: MedComm (2022)

Abstract Metastasis is the most prevalent cause of cancer deaths, and immunological components of the tumor microenvironment, especially tumor‐associated macrophages (TAMs), play a vital role in cancer metastasis. However, the underlying mechanisms of TAMs on non‐small‐cell lung cancer (NSCLC) metastasis remain largely unexplored. Herein, we demonstrated that M2‐like TAMs facilitate the migration and invasion of cancer cells in vitro and in vivo through intercellular delivery of M2‐like macrophage‐derived exosomes (M2‐exos). Importantly, we found that M2‐exos had considerably higher levels of integrin (ITG) αV and β3. The impact of M2‐like macrophage‐mediated invasion and migration of NSCLC cells was clearly decreased when ITG αVβ3 was blocked. Mechanistically, exosomal ITG αVβ3 produced from M2‐like macrophages successfully triggered the focal adhesion kinase signaling pathway in recipient cells, boosting the migratory and invasive abilities of NSCLC cells. Clinically, we found that metastatic NSCLC patients had greater ITG αV and β3 expression, which was associated with a worse prognosis. This study reveals a novel mechanism by which M2‐exos significantly increased NSCLC cell migration and invasion by delivering integrin αVβ3. Exosomal ITG αVβ3 can be used as a potential prognostic marker, and blocking ITG αVβ3 could be a viable treatment option for preventing tumor metastasis.
The effect of population-based blood pressure screening on long-term cardiometabolic morbidity and mortality in Germany: A regression discontinuity analysis
Authors: Sara Pedron, Michael Hanselmann, Jacob Burns, Alexander Rich, Annette Peters, Margit Heier, Lars Schwettmann, Jacob H. Bor, Till Bärnighausen, Michael Laxy
Journal: PLoS Medicine (2022)

Background Hypertension represents one of the major risk factors for cardiovascular morbidity and mortality globally. Early detection and treatment of this condition is vital to prevent complications. However, hypertension often goes undetected, and even if detected, not every patient receives adequate treatment. Identifying simple and effective interventions is therefore crucial to fight this problem and allow more patients to receive the treatment they need. Therefore, we aim at investigating the impact of a population-based blood pressure (BP) screening and the subsequent “low-threshold” information treatment on long-term cardiovascular disease (CVD) morbidity and mortality. Methods and findings We examined the impact of a BP screening embedded in a population-based cohort study in Germany and subsequent personalized “light touch” information treatment, including a hypertension diagnosis and a recommendation to seek medical attention. We pooled four waves of the KORA study, carried out between 1984 and 1996 ( N = 14,592). Using a sharp multivariate regression discontinuity (RD) design, we estimated the impact of the information treatment on CVD mortality and morbidity over 16.9 years. Additionally, we investigated potential intermediate outcomes, such as hypertension awareness, BP, and behavior after 7 years. No evidence of effect of BP screening was observed on CVD mortality (hazard ratio (HR) = 1.172 [95% confidence interval (CI): 0.725, 1.896]) or on any (fatal or nonfatal) long-term CVD event (HR = 1.022 [0.636, 1.641]) for individuals just above (versus below) the threshold for hypertension. Stratification for previous self-reported diagnosis of hypertension at baseline did not reveal any differential effect. The intermediate outcomes, including awareness of hypertension, were also unaffected by the information treatment. However, these results should be interpreted with caution since the analysis might not be sufficiently powered to detect a potential intervention effect. Conclusions The study does not provide evidence of an effect of the assessed BP screening and subsequent information treatment on BP, health behavior, or long-term CVD mortality and morbidity. Future studies should consider larger datasets to detect possible effects and a shorter follow-up for the intermediate outcomes (i.e., BP and behavior) to detect short-, medium-, and long-term effects of the intervention along the causal pathway.
Contemporary Biological Insights and Clinical Management of Craniopharyngioma
Authors: John Richard Apps, Hermann Lothar Muller, Todd Cameron Hankinson, Torunn Ingrid Yock, Juan Pedro Martinez-Barbera
Journal: Endocrine Reviews (2022)

Abstract Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close to the optic pathways, hypothalamus, and pituitary gland, such as increased intracranial pressure, endocrine deficiencies, and visual defects. Treatment is not specific and mostly noncurative, and frequently includes surgery, which may achieve gross total or partial resection, followed by radiotherapy. In cystic tumors, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in PCP, but also now in ACP and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumor and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients who bear tumors with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome, hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of CP, with emphasis on recent advances in the understanding of tumor pathogenesis, clinical consequences, management, and therapies.
Molecular Pathways and Mechanisms of HER2 in Cancer Therapy
Authors: Kanwal P.S. Raghav, Mark M. Moasser
Journal: Clinical Cancer Research (2022)

The oncogene ERBB2 encoding the receptor tyrosine-protein kinase erbB-2 (HER2) is frequently overexpressed or amplified and occasionally mutated in a variety of human cancers. The early discovery of this oncogene, its established oncogenic relevance in diverse cancers, its substantial expression on the surface of cancer cells, and its druggable catalytic activity have made it one of the most pursued targets in the history of cancer drug development. Initiatives targeting HER2 provided the early stimulus for several transformational pharmaceutical technologies, including mAbs, tyrosine kinase inhibitors, antibody-drug conjugates, and others. The seismic impact of these efforts has been felt in treatment of many cancers, including breast, gastroesophageal, lung, colorectal, and others. This impact continues to broaden with increasing indications on the horizon and a plethora of novel agents in development. However, implementation of these therapeutic strategies has been complex. The clinical translation of every one of these classes of agents has been notable for underperformance or overperformance characteristics that have informed new lines of research providing deeper insights into the mechanistic complexities and unrealized opportunities provided by this molecular target. Despite all the successes to date, the preponderance of scientific evidence indicates that the full potential of HER2 as a target for cancer therapeutics is far greater than currently realized, and numerous lines of investigation are ongoing to deepen and broaden the scope of impact of HER2 as a signaling, homing, or immunologic target. In this review, we explore the existing data and evolving paradigms surrounding this remarkable target for cancer therapy.
IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement by simultaneously binding to CD47 and CD20 of B cells
Authors: Jifeng Yu, Song Li, Dianze Chen, Dandan Liu, Huiqin Guo, Chunmei Yang, Wei Zhang, Li Zhang, Gui Zhao, Xiaoping Tu, Liang Peng, Sijin Liu, Xing Bai, Yongping Song, Zhongxing Jiang, Ruliang Zhang, Wenzhi Tian
Journal: Leukemia (2022)
ACE1 rs1799752 polymorphism is not associated with long-COVID symptomatology in previously hospitalized COVID-19 survivors
Authors: César Fernández-de-las-Peñas, Lars Arendt-Nielsen, Gema Díaz-Gil, Antonio Gil-Crujera, Stella M. Gómez-Sánchez, Silvia Ambite-Quesada, Maria A. Palomar-Gallego, Oscar J. Pellicer-Valero, Rocco Giordano
Journal: Journal of Infection (2022)
Mental Health Revisits at US Pediatric Emergency Departments
Authors: Anna M. Cushing, Danica B. Liberman, Phung K. Pham, Kenneth A. Michelson, Ara Festekjian, Todd P. Chang, Pradip P. Chaudhari
Journal: JAMA Pediatrics (2022)

Importance Pediatric emergency department (ED) visits for mental health crises are increasing. Patients who frequently use the ED are of particular concern, as pediatric mental health ED visits are commonly repeat visits. Better understanding of trends and factors associated with mental health ED revisits is needed for optimal resource allocation and targeting of prevention efforts. Objective To describe trends in pediatric mental health ED visits and revisits and to determine factors associated with revisits. Design, Setting, and Participants In this cohort study, data were obtained from 38 US children’s hospital EDs in the Pediatric Health Information System between October 1, 2015, and February 29, 2020. The cohort included patients aged 3 to 17 years with a mental health ED visit. Exposures Characteristics of patients, encounters, hospitals, and communities. Main Outcomes and Measures The primary outcome was a mental health ED revisit within 6 months of the index visit. Trends were assessed using cosinor analysis and factors associated with time to revisit using mixed-effects Cox proportional hazards regression. Results There were 308 264 mental health ED visits from 217 865 unique patients, and 13.2% of patients had a mental health revisit within 6 months. Mental health visits increased by 8.0% annually (95% CI, 4.5%-11.4%), whereas all other ED visits increased by 1.5% annually (95% CI, 0.1%-2.9%). Factors associated with mental health ED revisits included psychiatric comorbidities, chemical restraint use, public insurance, higher area measures of child opportunity, and presence of an inpatient psychiatric unit at the presenting hospital. Patients with psychotic disorders (hazard ratio [HR], 1.42; 95% CI, 1.29-1.57), disruptive or impulse control disorders (HR, 1.36; 95% CI, 1.30-1.42), and neurodevelopmental disorders (HR, 1.22; 95% CI, 1.14-1.30) were more likely to revisit. Patients with substance use disorders (HR, 0.60; 95% CI, 0.55-0.66) were less likely to revisit. Conclusions and Relevance Markers of disease severity and health care access were associated with mental health revisits. Directing hospital and community interventions toward identified high-risk patients is needed to help mitigate recurrent mental health ED use and improve mental health care delivery.
Functionally impaired antibody response to BNT162b2 booster vaccination in CVID IgG responders
Authors: Kai M.T. Sauerwein, Christoph B. Geier, Roman F. Stemberger, Raphael Rossmanith, Hüseyin Akyaman, Peter Illes, Michael B. Fischer, Martha M. Eibl, Jolan E. Walter, Hermann M. Wolf
Journal: Journal of Allergy and Clinical Immunology (2022)
Gabapentin Will Not Cure the Opioid Crisis
Authors: Audrey Han, Raegan W. Durant
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Selective Nanoblocker of Cellular Stress Response for Improved Drug‐Free Tumor Therapy
Authors: Cuimei Liu, Sihang Cheng, Xue Zhou, Jue Wang, Ping Mu, Zhongyao Wang, Lingyu Zhang, Lu Li, Chungang Wang
Journal: Advanced Healthcare Materials (2022)

Nanotechnology-based drug-free therapeutic systems using external stimuli can avoid the inherent side effects of drugs and become an attractive therapeutic strategy. However, the cellular stress responses (CSR) are activated encounter with external stimuli, which greatly weaken the efficacy of the drug-free antitumor. Thus, this work proposes a CSR regulation strategy and synthesizes the glucose oxidase (GOx)-modified Cu3 BiS3 nanosheets (CBSG NSs) encapsulated by calcium carbonate (CBSG@CaCO3 ) as the novel drug-free nanoagent. The CBSG@CaCO3 not only cause external stimuli such as energy consumption and oxidative stress damage, but also can destroy the CSR mechanism to guarantee optimal efficacy of starvation-chemodynamic therapy (ST-CDT). In tumor cells, the CaCO3 shell layer of CBSG@CaCO3 is rapidly degraded, releasing the slowly degradable CBSG NSs with NIR-II photothermal properties that accelerate the production of external stimuli under laser irradiation. Meanwhile, CaCO3 can block CSR to disrupt the adaptive viability of cancer cells by inhibiting expression of P27 and NRF2. Importantly, the CSR regulation achieves selective treatment on tumor cells based on the difference in physiological conditions between cancer cells and normal cells. This drug-free cancer therapy with selectivity improves the problem of poor efficacy under the action of CSR, which offers a new avenue in the cancer-related disease treatment.
Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age
Authors: Mikael Dellborg, Kok Wai Giang, Peter Eriksson, Hans Liden, Maria Fedchenko, Anders Ahnfelt, Annika Rosengren, Zacharias Mandalenakis
Journal: Circulation (2022)

Background: The survival of children with congenital heart disease has increased substantially over the past decades, with 97% currently reaching adulthood. The total effect of advanced treatment on future mortality and morbidity in adult survivors with congenital heart disease (CHD) is less well described. Methods: We used data from the Swedish National Inpatient, Outpatient, and Cause of Death Register to identify patients with CHD who were born between 1950 and 1999 and were alive at 18 years of age. Ten controls identified from the Total Population Register were matched for year of birth and sex and with each patient with CHD. Follow-up was from 1968 and 18 years of age until death or at the end of the study (2017). Survival percentage with 95% CI for all-cause mortality were performed with Kaplan-Meier survival function. Cox proportional hazard regression models with hazard ratios (HRs) and 95% CI were used to estimate the risk of all-cause mortality. Results: We included 37 278 patients with adult CHD (ACHD) and 412 799 controls. Mean follow-up was 19.2 years (±13.6). Altogether, 1937 patients with ACHD (5.2%) and 6690 controls (1.6%) died, a death rate of 2.73 per 1000 person-years and 0.84 per 1000 person years, respectively. Mortality was 3.2 times higher (95% CI, 3.0–3.4; P &lt;0.001) among patients with ACHD compared with matched controls. Up to the maximum of 50 years of follow-up, &gt;75% of patients with ACHD were still alive. Mortality was highest among patients with conotruncal defects (HR, 10.13 [95% CI, 8.78–11.69]), but also significantly higher for the more benign lesions, with the lowest risk in patients with atrial septal defects (HR, 1.36 [95% CI, 1.19–1.55]). At least 75% of patients with ACHD alive at 18 years of age lived past middle age and became sexagenerians. Conclusions: In this large, nationwide, register-based cohort study of patients with ACHD surviving to 18 years of age, the risk of mortality up to 68 years of age was &gt;3 times higher compared with matched controls without ACHD. Despite this, at least 75% of patients with CHD alive at 18 years of age lived past middle age and became sexagenerians. A notable risk decline in the mortality for patients with ACHD was seen for those born after 1975.
Documenting Racial Disparities or Disrupting Racism?
Authors: Leoandra Onnie Rogers, Nia Heard-Garris
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Annals Graphic Medicine - I Just … Don't Have the Time
Authors: Prathyusha Dasari
Journal: Annals of Internal Medicine (2022)

Web Exclusives27 December 2022Annals Graphic Medicine - I Just … Don't Have the TimeFREEPrathyusha Dasari, MSPrathyusha Dasari, MSUniversity of California, Riverside, School of Medicine, Riverside, California (P.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0021 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Prathyusha Dasari, MSAffiliations: University of California, Riverside, School of Medicine, Riverside, California (P.D.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0021.Author/Illustrator Information: Prathyusha Dasari, MS, is a third-year medical student at University of California, Riverside School of Medicine (e-mail, Prathyusha.Dasari@medsch.ucr.edu; LinkedIn, www.linkedin.com/in/dasari-prathyusha).This article was published at Annals.org on 27 December 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics January 2023Volume 176, Issue 1 ePublished: 27 December 2022 Issue Published: January 2023 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...